Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to apoptotic signals. However, the mechanisms underlying this process have not been resolved. We report that inactivation of the Caenorhabditis elegans AIF homolog wah-1 by RNA interference delayed the normal progression of apoptosis and caused a defect in apoptotic DNA degradation. WAH-1 localized in C. elegans mitochondria and was released into the cytosol and nucleus by the BH3-domain protein EGL-1 in a caspase (CED-3)-dependent manner. In addition, WAH-1 associated and cooperated with the mitochondrial endonuclease CPS-6/endonuclease G (EndoG) to promote DNA degradation and apoptosis. Thus, AIF and EndoG define a single, mitochondria-initiated apoptotic DNA degradation pathway that is conserved between C. elegans and mammals.
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PMID:Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. 1244 2

Zinc has been known for many years to inhibit apoptosis but the mechanism remains unclear. Originally thought to inhibit an apoptotic endonuclease, zinc has subsequently been shown to inhibit steps earlier in the pathway. Since many additional steps in apoptosis have now been defined, we have re-evaluated the steps inhibited by zinc. In response to activation of the chemical-mediated death pathway by anisomycin, 0.3 mM zinc inhibited Bax and Bak activation, cytochrome c release, and all of the subsequent steps in apoptosis. In the receptor-mediated death pathway initiated by Fas or tumor necrosis factor, 3 mM zinc was required to inhibit apoptosis as judged by inhibition of caspase 3 activity and DNA digestion, but it failed to inhibit cytochrome c release, activation of Bax and Bak, or upstream signaling events in this pathway. These results are consistent with zinc selectively inhibiting activation of BH3-only proteins required in the chemical pathway but inhibiting downstream caspase activation in the death-receptor pathway.
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PMID:Zinc inhibits Bax and Bak activation and cytochrome c release induced by chemical inducers of apoptosis but not by death-receptor-initiated pathways. 1276 74

Humans resist infection by the African parasite Trypanosoma brucei owing to the trypanolytic activity of the serum apolipoprotein L1 (APOL1). Following uptake by endocytosis in the parasite, APOL1 forms pores in endolysosomal membranes and triggers lysosome swelling. Here we show that APOL1 induces both lysosomal and mitochondrial membrane permeabilization (LMP and MMP). Trypanolysis coincides with MMP and consecutive release of the mitochondrial TbEndoG endonuclease to the nucleus. APOL1 is associated with the kinesin TbKIFC1, of which both the motor and vesicular trafficking VHS domains are required for MMP, but not for LMP. The presence of APOL1 in the mitochondrion is accompanied by mitochondrial membrane fenestration, which can be mimicked by knockdown of a mitochondrial mitofusin-like protein (TbMFNL). The BH3-like peptide of APOL1 is required for LMP, MMP and trypanolysis. Thus, trypanolysis by APOL1 is linked to apoptosis-like MMP occurring together with TbKIFC1-mediated transport of APOL1 from endolysosomal membranes to the mitochondrion.
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PMID:Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1. 2630 71